WO2009016309A2

WO2009016309A2 - Device for packaging and sublingual administration of active principles

Info

Publication number: WO2009016309A2
Application number: PCT/FR2008/051368
Authority: WO
Inventors: Philippe Perovitch
Original assignee: Philippe Perovitch
Priority date: 2007-07-20
Filing date: 2008-07-18
Publication date: 2009-02-05
Also published as: JP5912252B2; BRPI0812990A2; DK2182908T3; PL2182908T3; JP2010534081A; WO2009016309A3; HUE028682T2; EP2182908A2; ES2562667T3; US20100198147A1; RU2471474C2; CN101742984A; FR2918874A1; EP2182908B1; PT2182908E; RU2010106050A; CN101742984B; US8376988B2; FR2918874B1

Abstract

The invention relates to a container for the preparation and/or administration of a very small volume of active principles in liquid form, comprising a head (12) that is able to assume a first position P1 or storage position, in which said head (12) is in a distal position with respect to the container, and a second position P2 or administration position, in which said head (12) is in a proximal position with respect to the container, this head (12) comprising a cannula (14) with at least one flow channel (16), the length being adapted such that, with the container being held in the hand, the free end of the flow channel (16) is able to permit delivery by sublingual and/or gingival permeation.

Description

DEVICE FOR CONDITIONING AND SUBLINGUAL ADMINISTRATION OF ACTIVE PRINCIPLES

The present invention relates to a device for conditioning and administration of mucous active ingredients.

There are methods of diffusion of active principles by sublingual and / or para-gingival permeation that offer many advantages. Indeed, these diffusion methods allow to obtain much faster actions, with much lower dosages of active ingredients and more targeted by eliminating many side effects. These side effects are notably caused by the fact that the drugs to be administered orally are metabolized by the various digestive organs before diffusing towards the targets targeted by the active ingredients. Although this mucosal administration route is particularly attractive, it nevertheless remains linked to constraints that must be overcome to allow easy implementation by patients.

The active ingredients dissolved in solution, especially dissolved in alcoholic solutions, must be packaged in single doses, said conditioning must also allow a mucosal administration either sub-lingual or parapingival.

A first constraint is the extremely small volume of the dose to be administered, of the order of 0.25 ml to 2 ml to give an order of magnitude. The solution is also fragile with regard to light and / or air with oxidation phenomena and sensitive to evaporation phenomena. This solution can also be the subject of adsorption or ionization phenomena at contact with the walls of the container, hence the need to resort to inert and particularly protective materials.

However, the solution, in particular in the case of alcoholic solutions, must maintain its alcohol content and constant dissolution stability of the conditioned active ingredient (s), which parameters are adapted for optimized permeation. In addition, the alcoholic degree is adjusted to retain the active ingredients themselves.

It is important to maintain the alcoholic degree initially planned. In addition, for certain unstable pharmacological substances, their dissolution must be practiced only extemporaneously, at the very moment of administration, otherwise they would be altered, therefore inactive. An omnipresent constraint for such a single-dose packaging is the manufacturing cost, which must be extremely reduced in view of the number of packages to be produced and because of a single use in principle. Its recycling after use should also be promoted. Nevertheless, the packaging must maintain the requirements of safety, asepsis, in addition to the practicality and ergonomics sought to ensure easy provision self-medication.

This is why the present invention is directed to a container for the preparation and / or administration of a very small volume of active principles in liquid form comprising a head capable of taking a first storage position in which said head is in a distal position. relative to the container and a second administration position in which said head is proximal to the container, said head having a cannula, has at least one flow channel, the length being adapted so that the end Free flow channel can allow delivery by sublingual and / or para-gingival permeation, the container being held by hand. Very low volume means a volume to be administered between 0.1 and 5 ml.

This device is particularly suitable for the preparation and administration of active principles and / or antigenic substances for the purpose of pharmaceutical treatment, homeopathic and / or allergic desensitization.

The packaging according to the present invention is now described in detail according to a particular embodiment, not limiting, with reference to the attached drawings, drawings in which the different figures represent:

FIG. 1: a side perspective view of the packaging according to the present invention,

FIG. 2A: a sectional view of the packaging according to the present invention, before any use, ready for use,

- Figure 2B: a sectional view of the packaging according to the present invention, after implementation of the various means for its use, ready for immediate therapeutic administration,

FIG. 3: conditioning with a handling and handling pallet arranged in the lower part,

FIG. 4: a sectional view of a variant of the packaging according to the present invention, comprising several compartments, and

FIGS. 5A to 5C: a block diagram of a schematic variant of the packaging according to the present invention.

In Figure 1, there is shown a container 10 which can be in any material avoiding evaporation through the wall and able to avoid the action of light on the contents.

Such a container may be made of any material suitable for the packaged substances and the intended applications, such as glass, metal, plastic or a combination of these materials. The container is preferably glass, preferably thick glass, opacified, pharmaceutical grade, with high mechanical strength, square, oval, rectangular, triangular or round. In order to make the drawings explicit, the proportion of the scales is deliberately not respected.

This container 10 comprises a head 12 secured at least in translation relative to said container.

This head is capable of taking a first position P1 in which said head 12 is distal to the container 10 and a second position of administration P2 in which said head 12 is proximal to the container 10.

The head 12 comprises a cannula 14, with at least one flow channel 16. The length is adapted so that the free end of the flow channel 16 can be housed in particular under the language of the user or paragingival, the container being held by hand.

The cannula 14 comprises in addition to the flow channel 16, at least one air intake 18, for example a second channel 20. This second channel 20 may be coaxial and external or juxtaposed with the first channel 16 for example. The air intake can also be effected by the same first channel, according to its diameter, the liquid solution being a solution based on alcohol, so very low viscosity. This cannula 14 has at its free end a mouthpiece cover 22. This mouthpiece cover 22 is a sealed safety cap for example sealed and rotatably breakable for the best mode, or by traction or cutting. The cannula 14 is integral with the head 12 and advantageously come from manufacture with said head. The material may be a suitable polymeric material. The cannula 14 comprises at the bottom 24 perforation means. The container 10 and the head 12 are equipped with means 26 for translational movement of said head 12 from the distal position to the proximal position. The container is also provided with safety locking means 28 so as to prevent any involuntary displacement, in translation, of the head 12 relative to the container 10.

In the preferred embodiment, the translational displacement means 26 comprise a set of screws 30 carried by the container 10, more particularly by the neck 32 of this container and a thread 34 of the conjugate profile of the thread of the container carried. by the head 12 so as to cooperate by screwing.

The locking means 28 comprise a removable ring 36 interposed between the head 12 in a distal position and the container 10, more particularly the shoulder 38 of this container when it is provided with it, as shown in the embodiment of FIGS. 1 and 2.

This ring 36 has a profile in Ç which is elastically mounted on the thread 30 carried by the container 10, prohibiting the translational movement of the head 12 relative to the container 10.

In a complementary manner, the opening of the neck 32 of the container 10 is provided with a seal 40 which is tight and capable of being perforated by the perforation means 24. Advantageously, in order to ensure administration of the entire drug composition in liquid form, the head 12 comprises means 42 of total flow. These flow means 42 comprise, in part internally, a conical bottom, the cannula 14 being provided, in addition to the means 24 for perforation, holes 44 of passage, arranged immediately upstream of the bottom with respect to the direction of flow, in connection with the flow channel 16. In this case, the perforation means 24 comprise only a tip. Thus, the container 10 is filled with the medication composition in liquid form with mucous administration and then the container 10 is closed in a sealed manner by the laying of the cap 40 which also acts as a waterproofing membrane, especially in the case of an alcoholic solution. The ring 36 is disposed on the neck, around the screw thread 30, then the head 12 is attached by screwing until it comes into abutment on the ring 36.

The mouthpiece cover 22 is in place on the cannula 14, closing the flow channel 16 and the channel 20 of the air intake 18.

In this conservation position, the packaging is not usable and can be preserved, without altering the content and without risk of accessibility to young children.

When the user wishes to administer or administer the drug composition, it suffices to remove the ring 36 by simply pulling and screwing the head 12.

There then occurs a displacement in translation of said head which causes the perforating means to tear the lid which ensured the seal, allowing the liquid to flow to the cannula when the container is returned.

The removal of the mouthpiece 22 before reversal, for example by rotation causing the separation of this nozzle, allows to deliver the composition by the end of the cannula 14 positioned under the tongue or between the gum and the tongue or between the plays and the gum, the length of the cannula 14 being adapted for this purpose.

Thus, the composition is dispensed exactly where the efficiency is optimal, this for the entire volume contained.

It is noted that the air intake ensures a rapid distribution of the volume, which even low must be dispensed in a very short time, of the order of one second to give an order of magnitude.

For this purpose, the internal diameter of the flow channel 16 must be relatively large, of the order of 2 millimeters for the amounts mentioned above, between 0.25 and 2 ml. This proportionally large diameter can also ensure the return of air to facilitate rapid flow. In the case of using a container of the thick glass bottle type, it is possible to resort to a particular arrangement.

Either the neck carries a screw thread 30 come from manufacture with the container, or the neck is smooth. In the case of a smooth neck, the displacement means incorporate a ferrule which is directly fixedly attached to said neck of the container, for example by crimping, said ferrule carrying the screw thread 30 necessary to cooperate with the thread 34 of the head 12.

In this case, the glass container is filled with the composition and then capped.

Then, the ferrule is attached to the neck and crimped, then the ring 36 is positioned and the head 12 is put in place in turn.

For use, the user acts exactly as indicated above.

As has just been described, the dimensions of the bottle have been maximized to reveal the details of constitution but it must be taken into account that a container of 0.25 to 2 ml is extremely small and difficult to manipulate.

Also the present invention proposes an improvement to the container which consists of adding a pallet 46 for gripping, advantageously disposed in the lower part of the body of the container 10.

This pallet 46 gripping allows a good grip bidigital, despite the small size of the container to allow the user to maneuver the head 12 in rotation.

Similarly, this head 12 may comprise on its outer peripheral surface 48 gripping means such as fins 50, shown in the drawings.

The user is thus ready to maneuver by exerting a torque between the container 10 and the head 12.

Note also that the pallet 46 has a further handling advantage after rotation of the head relative to the container and after withdrawal of the mouthpiece cover, that of allowing easy handling of the container ready for use to position the cannula 14 at the desired location.

Alternatively, the ring 36 may be a plastic belt adapted to be torn or dessertie. To facilitate these belt removal operations, a prehensile external pull tab can be added to this belt.

Similarly, the filling before laying the lid can be performed under an inert gas atmosphere to preserve the contents.

According to another variant of the invention shown in FIG. 4, the container 10 comprises at least two compartments 52, each compartment being separated by a sealed cover 54.

Each compartment contains at least one active ingredient, an excipient, an antigenic substance and / or a solvent.

The device also comprises perforation means 24 capable of tearing the lids 40 and / or 54, preferably arranged at the foot of the cannula 14 and / or in contiguity of the compartments 52 so as to obtain mixtures of the substances in a given order .

When the user wishes to administer or administer the drug composition, he removes the ring 36 by traction and then screws the head 12. There then occurs a displacement in translation of said head which causes the perforating means to tear the lid or lids 40 and / or 54, allowing the substances contained in each compartment 52 to mix to obtain a liquid flowing to the cannula when the container is returned.

The head 12 may also contain an active principle, an excipient, an antigenic substance and / or a solvent, for example at the level of the cannula 14. The head 12 may also have several compartments separated by a cap 66.

The substance contained in the head 12 may be in the form of powder, tablet, lyoc, liquid microcapsule, etc. When the head moves in translation, the perforating means tear the lid (s) 40 and / or 54 and / or 66 allowing the substances contained in the head 12, in particular in the cannula 14, and in each compartment 52 to mix. Similarly, if the substance contained in the head 12 is encapsulated, the perforation means tear the membrane encapsulating said substance before perforating the or lids 40 and / or 54 and / or 66.

The substance contained in the head 12 may also be in the form of a liquid contained in the cannula 14 of the head 12, as shown in FIG. 5. The cannula 14 then comprises an upper portion 56 enclosing the liquid sealed by a lid 62, and a lower portion 58, separated by a thread 60. A first rotation of the head 12 on the thread 30 causes the portion 58 to tear the seal 40 which sealed the container 10. A rotation additional causes the stop portion 58 on the thread 30. The cannula 14 then rotates around the second thread 60, which allows to tear the seal 62 which sealed the cannula. The liquid of the head 12 is thus released and the substances that were separated can mix. These forms of container according to the invention has at least two compartments 52 and / or a head 12 containing one or more substances, are particularly suitable for active ingredients and unstable substances in solution. This is the case, for example, with lipophilic active principles, which, although perfectly soluble in hydroalcoholic solutions, exhibit unstable evolutions with risks of denaturation and formation of undesirable compounds. The container according to the invention makes it possible to protect the active principle, excipient and / or antigenic substance in the form of powder, lyoc, tablet, liquid microcapsule, etc., and to carry out an extemporaneous dissolution in a solvent just before the administration. It is thus possible for certain complex and mutable components to form a device with several separate compartments for a successive assembly of these different substances not compatible just before their administration, this in a determined order.

The container according to the invention can be used for the preparation and / or the administration of active principles and / or antigenic substances for the purposes of pharmaceutical treatment, homeopathic and / or allergic desensitization, in particular by the transmucosal route.

Claims

1. Container (10) for the preparation and / or administration of a very small volume of active ingredients in liquid form comprising a head (12) adapted to take a first storage position P1 in which said head (12) is in a distal position with respect to the container (10) and a second position of administration P2 in which said head (12) is in a position proximal to the container (10), this head (12) comprising a cannula (14), with at least one flow channel (16), the length being adapted so that the free end of the flow channel (16) can allow for sub-lingual and / or para-gingival permeation delivery, the container being held in the hand.

2. Container (10) for the preparation and / or administration of a very small volume of active ingredients in liquid form according to claim 1, characterized in that it comprises means (26) for translational movement of the head (12), these means comprising a set of screws (30) carried by said container 10, and a thread (34) of conjugated profile of the screw thread of the container carried by the head (12) so as to cooperate by screwing .

3. Container (10) for the preparation and / or the administration of a very small volume of active principles in liquid form according to claim 1 or 2, characterized in that it comprises means (28) of security lock so as to prevent any involuntary displacement, in translation, of the head (12) relative to the container (10).

4. Container (10) for the preparation and / or administration of a very small volume of active ingredients in liquid form according to claim 3, characterized in that the means (28) for locking comprise a ring (36) removable interposed between the head (12) distally and the container (10).

5. Container (10) for the preparation and / or administration of a very small volume of active principles in liquid form according to any one of the preceding claims, characterized in that the cannula (14) is provided with a mouthpiece cover (22) safety, breakable.

6. Container (10) for the preparation and / or administration of a very small volume of active principles in liquid form according to any one of the preceding claims, characterized in that it comprises a neck (32) and in the opening of this neck is provided with a seal (40) sealed.

7. Container (10) for the preparation and / or administration of a very small volume of active principles in liquid form according to any one of the preceding claims, characterized in that it comprises at least two compartments (52) each compartment being separated by a sealed cover (54).

8. Container (10) for the preparation and / or administration of a very small volume of active ingredients in liquid form according to claim 7, characterized in that each compartment (52) contains at least one active ingredient, an excipient , an antigenic substance and / or a solvent.

9. Container (10) for the preparation and / or administration of a very small volume of active principles in liquid form according to one of claims 6 to 8, characterized in that it comprises means (24) of perforation of the lid (s) 40 and / or 54.

10. Container (10) for the preparation and / or administration of a very small volume of active ingredients in liquid form according to claim 9, characterized in that the means (24) for perforation are arranged at the bottom of the cannula (14). ).

11. Container (10) for the preparation and / or administration of a very small volume of active ingredients in liquid form according to one of claims 7 or 8, characterized in that the means (24) of perforation are arranged at the foot of the cannula (14) and / or in contiguity of compartments (52) so as to obtain mixtures of the substances contained in said compartments in a determined order.

12. Container (10) for the preparation and / or administration of a very small volume of active ingredients in liquid form according to one of the preceding claims, characterized in that the head (12) comprises an active principle, a antigenic substance, an excipient and / or a solvent.

13. Container (10) for the preparation and / or administration of a very small volume of active ingredients in liquid form according to any one of the preceding claims, characterized in that it comprises a pallet (46) gripping disposed in the lower part of the body of the container (10) so as to allow a good grip bidigitale clamp.

14. Container (10) for the preparation and / or administration of a very small volume of active ingredients in liquid form according to any one of the preceding claims, characterized in that the head (12) has on its outer surface peripheral means (48) for gripping.

15. Container (10) for the preparation and / or administration of a very small volume of active principles in liquid form according to any one of the preceding claims, characterized in that it is suitable for the administration of principles active and / or antigenic substances for pharmaceutical, homeopathic and / or allergic desensitization purposes.

16. Container (10) for the preparation and / or administration of a very small volume of active ingredients in liquid form according to claim 15, characterized in that it is suitable for per mucosal administration.